A stent is a physical support in the form of a hollow mesh tube that is used in many cases to maintain adequate flow in body passages including cardiovascular, urethral, esophageal, biliary, prostatic or pancreatic vessels.
The geometrical design of a stent plays a major role in its strength, performance and elasticity. Design of stents aims at getting the highest radial resistive force possible and the lowest chronic outward force possible. A range of different stent patterns are known to the skilled person, and an appropriate pattern may be selected for a given use.
Traditionally, stents were fabricated of bare metals as platinum, chromium or stainless steel. However, the permanent presence of stents in the injury site after complete recovery of the vascular functioning leads to late complications including late stenosis and late lesion revascularization.1 Intensive research effort has been performed to develop more advanced stents as drug eluting stents. However, Post-Implementation Syndrome (PIS) is still a common complication of stent implementation which is defined as fever and transient elevation in inflammatory biomarkers. Mechanisms lying behind PIS are still unknown; however it seems related to the type of material used for fabrication of stents. As a result, efforts were directed to the development of bioresorbable stents (also referred to as biodegradable or bioabsorbable stents; the terms are used interchangeably herein) to avoid unnecessary presence of the stent after an adequate recovery period that may vary starting from about 6 months.
Several materials are currently used to fabricate cardiovascular stents. Among these materials are woven polyesters and expanded polytetrafluoroethylene. It was found that polytetrafluoroethylene induces less inflammation when compared to woven polyesters.2 A common metal stent is made of nitinol which is a mixture of nickel and titanium.
Conventional stents are unable to inhibit overgrowth of smooth muscle and extracellular matrix which eventually leads to narrowing of blood vessels. One of the approaches investigated to overcome such problem is to develop biodegradable stents. One of the most commonly used materials for biodegradable stents is polylactide which is degraded into water and CO2 and thus, its implementation is inert to the body. Magnesium is also used for biodegradable stents in the form of various alloys, with or without additional coatings to decrease the degradation rate. However, the use of biodegradable stents is still limited due to many unsettled considerations. These include for instance; 1—incomplete endothelialization which may lead to increased thrombosis, 2—fragmentation of the stent by partial degradation that may release particles that can induce thrombosis, and 3—severe inflammation or fibrosis that may block the stented area. On the other hand, early investigations regarding the use of biodegradable stents showed good biocompatibility with minimal complications.
The versatility of the polymers used in stents allowed the development of bioresorbable drug eluting stents which release various drugs including heparin, antithrombotic and anti-inflammatory agents. The first drug eluting stent was approved for clinical use in 2003 and it was composed of 50/50% mixture of poly(ethylene-co-vinylacetate) (PEVA) and poly(butyl methacrylate) (PBMA) which is a biostable stent and was loaded with sirolimus which is a potent immunosuppressant and antiproliferative agent.
Although antiproliferative drugs are commonly incorporated into drug eluting stents, they do not provide an optimal solution to prevent post-implementation stenosis. These drugs inhibit the overgrowth of smooth muscle cells; however they also inhibit the re-growth of endothelial cells and endothelium healing. Incomplete endothelium and its inability to heal lead to endothelium dysfuction and remodeling. This observation motivated the search for drug eluting stents that allow adequate endothelial recovery while inhibiting stenosis. Another key factor in stenosis is the adhesion of platelets on the stent surface since after platelet adhesion and aggregation, α-granules are released containing P-selectin which induces more aggregation and thrombus formation. Thus an important goal of designing stent materials is to inhibit platelet adhesion to its surface.